Fast single-channel measurements resolve the blocking effect of Cs+ on the K+ channel

Abstract

The Cs+ block of K+ channels has often been investigated by methods that allow only indirect estimation of the rate constants of blocking and re-opening. This paper presents single-channel records with high temporal resolution which make the direct observation of the fast transitions between the blocked and the unblocked state possible. The rate constants kOGb, kGbO of Cs(+)-dependent blocking and of re-opening are evaluated from the time constants found in the open-time and closed-time histograms. The blocking rate constant kOGb between 1000 and 50000 s-1 depends linearly on the Cs+ concentration and strongly on voltage, increasing by a factor of 1.44 per 10 mV hyperpolarization. The re-opening rate constant kGbO approximately 30000 s-1 is independent of Cs+ concentration and only slightly voltage-dependent. Formally, the results can be described by a Woodhull-model. The strong voltage dependence with d > 1, however, weakens its plausibility. The results are interpreted in terms of a molecular framework emerging from recent results on the structure of voltage-gated channels.